Anesthetized, paralyzed dogs were ventilated with a low inspired O2 fraction or were isovolemically hemodiluted until aerobic metabolism could not be supported at the prehypoxic level. O2 uptake became a single linear function of total O2 delivery (QxCaO2) in both anemic and hypoxic hypoxia. At the same time, mixed venous PO2 was significantly higher during anemic hypoxia than during hypoxic for a comparable level of reduction in O2 uptake. The objectives of the proposed research will be to ascertain whether the state of sympathetic vasoconstrictor tone in regional circulatory beds was responsible for both observations. In brief, stimulation of aortic and carotid chemoreceptors by low PO2 may increase sympathetic vasoconstrictor tone so that blood flow is selectively directed toward regions with a high obligatory level of O2 demand to maintain viability. This is accomplished by local vasodilatory processes which are directly proportional to the ratio of O2 delivery to O2 demand. In this manner, perfusion is matched to O2 demand and intercapillary distances are shortened so that O2 extraction is promoted, even at very low capillary PO2. In the case of anemic hypoxia, the normal to high PO2 may have only weakly stimulated chemoreceptors so that less sympathetic vasoconstrictor tone was present. Without vasoconstriction to work against, local regulation may have been ineffectual so that relative overperfusion of low O2 demand regions might have occurred. These possibilities will be tested by alpha-adrenergic blockers and agonists to alter sympathetic vasoconstrictor tone during anemic, stagnant, and hypoxic hypoxia. Regional differences in O2 extraction and venous PO2 will be sought as well as the regional contributions to whole body O2 deficit and mixed venous PO2. For example, venous PO2 is probably uniformly low in hypoxic hypoxia, but alpha-adrenergic blockage may cause it to rise and may cause regional differences to appear. In anemic hypoxia, norepinephrine infusion may cause regional differences in venous PO2 to diminish and O2 extraction may be increased. Similar approaches will be used in an isolated hindlimb preparation to delineate analagous alterations in regional tissue O2 delivery at the microvascular level.